Amount of calcium in the sarcoplasmic reticulum: influence on excitation-contraction coupling in heart muscle.
Real-time imaging of the concentration of intracellular calcium ([Ca2+]i) has been carried out in heart cells using confocal imaging and patch-clamp techniques. Here we review recent investigations that used genetically engineered mice that lack phospholamban (PL knockout) to investigate the mechanisms of excitation-contraction (EC) coupling in heart. The heart cells from PL knockout (KO) mice exhibit [Ca2+]i transients that are larger than normal. Similarly, the elementary units of EC coupling, called Ca2+ sparks, were found to be more frequent in PL KO heart cells than normal heart cells. This finding is consistent with the findings that cell-wide [Ca2+]i transients arise as Ca2+ sparks sum during the EC coupling process. Finally, it was determined that the amount of Ca2+ within the sarcoplasmic reticulum (SR) was greater in the PL KO cardiac myocytes than in controls. Analysis of the results indicate that the larger [Ca2+]i transients and the more frequent Ca2+ sparks are due to the greater amount of Ca2+ within the SR of PL KO myocytes, as the Ca2+ current (ICa), which triggers the Ca2+ sparks and the [Ca2+]i transient, was the same in control and PL KO heart cells. We conclude that the amount of Ca2+ released from the SR per unit of triggering ICa increases as the SR Ca2+ content is augmented. Regulation of SR Ca2+ content is thus a means by which cardiac contractility is regulated.
Santana
L F
LF
Department of Molecular Biology and Biophysics, University of Maryland School of Medicine, Baltimore 21201, USA.
Gómez
A M
AM
Kranias
E G
EG
Lederer
W J
WJ
D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry*; D000099211:Phospholamban
D002118:Calcium; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000099211:Phospholamban